Hydroxy-amide functionalized azolium salts for Cu-catalyzed asymmetric conjugate addition: stereocontrol based on ligand structure and copper precatalyst.

Naoatsu Shibata, Misato Yoshimura, Haruka Yamada, Ryuichi Arakawa, Satoshi Sakaguchi

Index: J. Org. Chem. 77(8) , 4079-86, (2012)

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Abstract

A series of hydroxy-amide functionalized azolium salts have been designed and synthesized for Cu-catalyzed asymmetric conjugate addition reaction. The (CH(2))(2)-bridged hydroxy-amide functionalized azolium ligand precursors 2, in addition to the previously reported CH(2)-bridged azolium salts 1, have been prepared from readily available enantiopure β-amino alcohols. The combination of a Cu species with 1 or 2 efficiently promoted the 1,4-addition reaction of cyclic enones with dialkylzincs. For example, the reaction of 2-cyclohepten-1-one (17) with Bu(2)Zn in the presence of catalytic amounts of Cu(OTf)(2) and 1 gave (S)-3-butylcycloheptanone (20) in 99% yield and 96% ee. On the other hand, when the reaction was carried out under the influence of Cu(OTf)(2) combined with 2, (R)-20 in preference to (S)-20 was obtained in 98% yield and 80% ee. In this manner, the enantioselecvity was switched by controlling the structure of chiral ligand. Additionally, the reversal of enantioselectivity was also achieved by changing the Cu precatalyst from Cu(OTf)(2) to Cu(acac)(2) with the same ligand. The combination of Cu(acac)(2) with CH(2)-bridged azolium salt 1 in the reaction of 17 with Bu(2)Zn led to formation of (R)-20 as a major product in 55% yield and 80% ee. This result was in contrast to the Cu(OTf)(2)/1 catalytic system, where the 1,4-adduct with opposite configuration was obtained. Moreover, use of the Cu(acac)(2)/2 catalytic system produced (S)-20, while (R)-20 was formed by the Cu(OTf)(2)/2 catalytic system. Thus, it was found that either varying the linker of the chiral ligands or changing the counterion of Cu species between a OTf and acac ligand initially on the metal led to dual enantioselective control in the 1,4-addition reaction.© 2012 American Chemical Society